Clinical colorectal cancer最新文献

{"title":"Impact of distal resection margin on survival after tumour-specific mesorectal excision for rectal cancer: retrospective cohort study","authors":"Fabio Carbone ,&nbsp;Roberto Santalucia ,&nbsp;Simona Borin ,&nbsp;Davide Ciardiello ,&nbsp;Luca Bottiglieri ,&nbsp;Stefano de Pascale ,&nbsp;Emilio Bertani ,&nbsp;Uberto Fumagalli Romario","doi":"10.1016/j.clcc.2025.08.001","DOIUrl":"10.1016/j.clcc.2025.08.001","url":null,"abstract":"<div><h3>Background</h3><div>The safe oncological distal resection margin (DRM) after anterior resection (AR) with tumour-specific mesorectal excision (TSME) for rectal cancer is still debated. This study aims to clarify the impact of DRM on survival outcomes.</div></div><div><h3>Methods</h3><div>Patients who underwent an intention-to-treat AR-TSME for a non-metastatic rectal adenocarcinoma within 15 cm from the anal verge from September 2018 to February 2024 were included. Those with locally advanced rectal cancer underwent neoadjuvant treatment. Patients were divided into 3 groups according to the DRM: &lt; 1 cm, 1 to 4.9 cm, and ≥ 5 cm, and compared for overall survival (OS) and disease-free survival (DFS).</div></div><div><h3>Results</h3><div>A total of 268 patients were included: 29 with DRM &lt; 1 cm (11%), 208 with DRM 1 to 4.9 cm (78%), and 31 with DRM ≥ 5 cm (11%). Median follow-up was 27 months. Three-year OS was 93%, 97%, and 100% in the respective groups (<em>P</em> = .36); DFS was 85%, 76%, and 75% (<em>P</em> = .51). Multivariable analysis did not identify DRM as an independent risk factor for OS or DFS. Circumferential resection margin (CRM) involvement (HR 4.68, 95%CI 1.78-12.31) and R1 resections (HR 5.66, 95%CI 2.31-13.87) were significantly associated with disease recurrence. Subgroup analysis showed no significant impact of DRM on the survival of patients undergoing neoadjuvant therapy.</div></div><div><h3>Conclusions</h3><div>Short DRM does not compromise oncological outcomes, provided that complete (R0) resection is achieved. These findings support a more individualised surgical approach, with emphasis on CRM status over arbitrary DRM thresholds.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 4","pages":"Pages 446-453.e9"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of Mismatch Repair Deficiency in Rectal Cancer and Response to Neoadjuvant Treatment","authors":"Jelle A. Nieuwstraten ,&nbsp;Eline G.M. van Geffen ,&nbsp;Martijn W.H. Leenders ,&nbsp;Pieter J. Tanis ,&nbsp;Miranda Kusters ,&nbsp;Tjeerd S. Aukema","doi":"10.1016/j.clcc.2025.09.001","DOIUrl":"10.1016/j.clcc.2025.09.001","url":null,"abstract":"<div><h3>Introduction</h3><div>The role of mismatch repair deficiency (dMMR) in colon cancer has gained increasing attention due to its association with response to neoadjuvant therapy. In contrast, its significance in rectal cancer remains less comprehensively explored. The influence of dMMR on pathological response following neoadjuvant (chemo)radiotherapy ((C)RT) in rectal cancer is not well understood. This study aimed to compare pathological response to neoadjuvant treatment between dMMR and proficient mismatch repair (pMMR) rectal cancer.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted using data from the Dutch ColoRectal Cancer Audit database, including patients who underwent rectal cancer resection between 2018 and 2021. Primary outcomes of this study were the incidence of dMMR and pathological complete response (pCR). A multinomial logistic regression analysis was performed to determine if MMR-status was an independent predictor of pCR.</div></div><div><h3>Results</h3><div>Out of 8570 patients, MMR-status was determined in 4659 (54.4%) patients, of whom 4516 (96.9%) were pMMR and 143 (3.1%) dMMR. A total of 1562 patients with known MMR-status underwent neoadjuvant treatment. 1514 (96.9%) had pMMR tumors and 48 (3.1%) dMMR tumors. The pCR rate was significantly higher in dMMR patients (29.2%) compared to pMMR patients (13.5%, <em>P</em> = .008). Multivariable logistic regression analysis showed that MMR-status was independently associated with pCR (OR 2.422 [95% CI, 1.236-4.746], <em>P</em> = .010).</div></div><div><h3>Conclusion</h3><div>In this cross-sectional national rectal cancer cohort, the incidence of dMMR was 3.1%, and dMMR appeared to be an independent predictor for higher chance of pathological complete response after neoadjuvant (chemo)radiotherapy.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 4","pages":"Pages 483-491"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Neoadjuvant Immunotherapy in Localized Rectal Cancer. A Systematic Review","authors":"Florian Salihu ,&nbsp;Claudia Corro ,&nbsp;Frédéric Ris ,&nbsp;Guillaume Meurette ,&nbsp;André Durham ,&nbsp;Vassilis Genoud ,&nbsp;Aurélie Bornand ,&nbsp;Jeremy Meyer ,&nbsp;Thibaud Koessler","doi":"10.1016/j.clcc.2025.08.005","DOIUrl":"10.1016/j.clcc.2025.08.005","url":null,"abstract":"<div><div>Current treatments for locally advanced rectal cancer (LARC) include preoperative radiotherapy, chemotherapy and chemoradiotherapy followed by total mesorectal excision (TME), which can severely impact quality of life. Recently, anti-PD1 immunotherapy in microsatellite instability high (MSI-H) LARC has shown 100% clinical complete responses, allowing patients to avoid surgery with minimal toxicity. This review assesses the safety, toxicity, pathological impact, and long-term benefits of incorporating immunotherapy into the neoadjuvant treatment of microsatellite stable (MSS) and MSI-H LARC.</div><div>This systematic review, conducted following PRISMA guidelines, investigates neoadjuvant immunotherapy in LARC. Data on study characteristics, treatment protocols, and outcomes were extracted. Quality assessment was conducted by using the Methodological Index for nonrandomized studies (MINORS) and the RoB2 tool. Patients were categorized into MSI-H, MSS, and unknown microsatellite status cohorts.</div><div>We found twelve published studies including 547 patients. In the MSS cohort, postneoadjuvant surgery rates ranged from 57.6% to 100%, with a watch-and-wait approach adopted in up to 27.1% of cases. For MSI-H patients, surgery and watch-and-wait rates varied widely (0%-100%), reflecting heterogeneity in management. R0 resection rates were high across cohorts (70%-100% MSS, 80%-100% MSI-H). Pathological complete response (pCR) rates were 25% to 50% in MSS and 50% to 60% in MSI-H cohorts. Grade 3–4 adverse events ranged from 3.9% to 45.2% (MSS), 0% to 60% (MSI-H), with immune-related events generally below 10%.</div><div>The role of immunotherapy in MSS rectal cancer remains unclear; phase III trials and translational research are needed urgently for guidance</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 4","pages":"Pages 425-431.e1"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B7-H3 in Colorectal Adenocarcinoma: Are We Focusing on the Right Target?","authors":"Paola Parente ,&nbsp;Davide Ciardiello ,&nbsp;Valentina Angerilli ,&nbsp;Jessica Gasparello ,&nbsp;Matteo Fassan","doi":"10.1016/j.clcc.2025.09.005","DOIUrl":"10.1016/j.clcc.2025.09.005","url":null,"abstract":"<div><h3>Introduction</h3><div>B7-H3 belongs to B7 protein family which comprises molecules located on the cell surface, that play a crucial role in the modulation of immune response. Emerging data suggest that B7-H3 could promote cancer progression by coinhibitory effects on T cell responses, allowing cancer cells to avoid immune response, favoring invasion, metastatic spread, and drug resistance. Nevertheless, conflicting data regarding B7-H3 tumor expression, clinical correlation, and therapy response are reported. This is mainly due to (1) different investigated populations, (2) methods employed to assess its expression, and (3) the lack of standardized guidelines for B7-H3 expression scoring.</div></div><div><h3>Materials and Methods</h3><div>We investigated, on the whole sections, the immunohistochemical expression of B7-H3 (clone D9M2L) in a cohort of 87 patients affected by localized colorectal cancer (CRC, stage I-III), retrospectively selected to be representative of the different CRC histotypes, according to WHO, 2019 edition.</div></div><div><h3>Results</h3><div>Positive B7-H3 staining was documented in 68/89 cases (76.5%). All 68 cases showed immunostaining in neoplastic stroma, whereas non-neoplastic tissue was unstained in all 55 cases with normal mucosa and in 5 cases of dysplasia (100%). The highest frequency of B7-H3 positivity was observed in the CRC, NOS histotype (86%). The positivity rate in NOS histotype is even higher (90.5%), when only low-grade cases are considered, whereas lower rates (73.3%) were reported in the high-grade subgroup.</div></div><div><h3>Conclusion</h3><div>The presented data provide further evidence on the role of B7-H3 in CRC with particular reference to the tumor microenvironment and histotype, with a possible implication for the CRC therapy. Further studies are required to both confirm these data and elucidate the role of B7-H3 as a potential target to unleash the response to immunotherapy in CRC.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 4","pages":"Pages 492-497"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Total Neoadjuvant Treatment on Pathological Response and Survival in Locally Advanced Rectal Cancer: A Single Center Experience","authors":"Okan Aydın ,&nbsp;Ahmet Emin Öztürk ,&nbsp;Mert Erciyestepe ,&nbsp;Şermin Dinç Sonuşen ,&nbsp;Zehra Sucuoğlu İşleyen ,&nbsp;Selvi Tabak Dinçer ,&nbsp;Emir Çelik ,&nbsp;Kayhan Ertürk ,&nbsp;Muhammed Mustafa Atcı","doi":"10.1016/j.clcc.2025.05.001","DOIUrl":"10.1016/j.clcc.2025.05.001","url":null,"abstract":"<div><h3>Background</h3><div><span>Total neoadjuvant therapy (TNT) has emerged as a promising approach in the treatment of locally advanced </span>rectal cancer<span> (LARC), aiming to improve pathological complete response (pCR) and survival by eradicating micrometastases.</span></div></div><div><h3>Purpose</h3><div>We aimed to evaluate the effect of TNT, which has been applied to patients with LARC in our clinic since 2019, on pathological response and survival and to present real-life data.</div></div><div><h3>Methods</h3><div><span>The medical records of 116 patients with stage 3 locally advanced </span>rectal cancer who were followed at our clinic between March 2019 and March 2024 and who received TNT were retrospectively analyzed. Patients with pCR and non-pCR and TRG 0-1 and 2-3 were compared.</div></div><div><h3>Results</h3><div><span>The median follow-up period was 24.5. All of these 116 patients, were stage 3 (mostly stage 3B). Surgery was performed in 106 patients after TNT and 10 patients (8.6%) were followed with nonoperative management (NOM). Pathological complete response (pCR) was achieved in 28 (26.5%) of these 106 patients. The number of CAP-TRG 1 patients (near-pCR) was 35 (33%) and the number of CAP-TRG 2-3 patients was 43 (40.5%). Complete and near-complete responses (pCR and near-pCR) were achieved in approximately 60% of patients. Two parameters showed statistical significance in the univariate analysis<span> of factors affecting pCR; tumor distance from the anal verge &gt; 10 cm increased pCR 7.2-fold (</span></span><em>P</em> = .02) and CEA level at diagnosis ≤ 5 ng/ml increased pCR 4.4-fold (<em>P</em><span> = .008). During follow-up, 10 patients developed recurrence and/or metastasis and 5 of these 10 patients died. The majority of treatment-related toxicities were manageable grade 1-2 toxicities.</span></div></div><div><h3>Conclusion</h3><div>These single center, real-world data provide a perspective on the impact of TNT on pathological response and survival in patients with LARC. TNT is an effective and safe treatment and has become the standard of care with increased pathological complete response rates.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 3","pages":"Pages 369-377.e1"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI Monitoring of Locally Advanced Rectal Cancer in Watch and Wait Patients","authors":"Jian Zhao ,&nbsp;Kanghua Huang ,&nbsp;Akao Zhu ,&nbsp;Jinghan Zhu ,&nbsp;Yimin Fang ,&nbsp;Xiaofeng Zhou ,&nbsp;Hao Jiang ,&nbsp;Li Shen ,&nbsp;Haiyan Chen","doi":"10.1016/j.clcc.2025.05.003","DOIUrl":"10.1016/j.clcc.2025.05.003","url":null,"abstract":"<div><h3>Background</h3><div>Watch and wait (W&amp;W) is an alternative strategy for locally advanced rectal cancer (LARC) (T3-4/N+) patients. MRI-based evaluation of clinical complete response (cCR) and post-cCR disease monitoring remain uncertain. This study aims to investigate the association between MRI feature changes and survival outcomes in these patients.</div></div><div><h3>Methods</h3><div>LARC Patients achieving cCR after neoadjuvant chemoradiotherapy and opting for W&amp;W were included. MRI features were recorded from pretreatment to the follow-up period, including tumor bed scarring on post-treatment T2-weighted imaging (T2WI), magnetic resonance tumor regression grade (mrTRG), and high-signal areas on diffusion-weighted imaging (DWI). The relationship between follow-up data and MRI feature changes over time was analyzed.</div></div><div><h3>Results</h3><div>41 patients were included, and 5-year PFS and OS were 64.1% and 90.9%. For the 11 patients without cCR at the initial assessment, tumor signals decreased over time on both T2WI and DWI, with an increasing trend in scar formation on T2WI. Cumulative cCR rates at 7 weeks (± 1 week), 16 weeks (± 3 weeks), 24 weeks (± 4 weeks), and 32 weeks (± 3 weeks) were 72.5%, 80.5%, 95.1%, and 100.0%. Seven patients (17.1%) had a recurrence, with a disruption of the scar and the appearance of intermediate-intensity signals within the low-signal fibrotic area of the original tumor bed on T2WI. A newly developed high-signal area was observed on DWI.</div></div><div><h3>Conclusions</h3><div>The cCR rate increased over time. The scar sign on T2WI was more prevalent in patients with cCR, increased over time. MRI surveillance is essential for W&amp;W patients but remains dynamic and challenging.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 3","pages":"Pages 378-388.e5"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Oligometastatic BRAFV600E Mutant Colorectal Cancer: Learning From a Clinical Case","authors":"Renato Maria Marsicano ,&nbsp;Luca Boscolo Bielo ,&nbsp;Elena Guerini Rocco ,&nbsp;Mariano Lombardi ,&nbsp;Emilio Bertani ,&nbsp;Filippo Maria Bassi ,&nbsp;Giuseppe Curigliano ,&nbsp;Davide Ciardiello ,&nbsp;Nicola Fazio ,&nbsp;Maria Giulia Zampino","doi":"10.1016/j.clcc.2025.03.003","DOIUrl":"10.1016/j.clcc.2025.03.003","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div><span><span>Treatment with Encorafenib plus </span>Cetuximab is one standard option of care in patients with </span><em>BRAF V600E</em><span>-mutated (MT) metastatic colorectal cancer (mCRC).</span></div></span></li><li><span>•</span><span><div>Treatment of oligometastatic disease in <em>BRAFV600E</em> MT CRC remains a topic of debate.</div></span></li><li><span>•</span><span><div>Here, we present the case of a patient with oligometastatic lymph nodes-only involvement treated with target therapy and loco-regional treatment.</div></span></li></ul></div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 3","pages":"Pages 410-414"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Neoadjuvant Chemotherapy Before Simultaneous Resection of Colon Cancer and Liver Metastases: A Propensity-Score Matched Analysis","authors":"Sameh Hany Emile ,&nbsp;Zoe Garoufalia ,&nbsp;Rachel Gefen ,&nbsp;Justin Dourado ,&nbsp;Ebram Salama ,&nbsp;Steven D. Wexner","doi":"10.1016/j.clcc.2025.05.005","DOIUrl":"10.1016/j.clcc.2025.05.005","url":null,"abstract":"<div><h3>Background</h3><div><span>There has been a controversy about the optimal management of colorectal liver metastases<span> (CLM). Both upfront surgery and neoadjuvant chemotherapy are viable options for CLM. The present study aimed to assess the short-term and survival outcomes of neoadjuvant chemotherapy before simultaneous resection of primary </span></span>colon cancer and liver metastases.</div></div><div><h3>Methods</h3><div>This retrospective cohort study<span> used data from the National Cancer Database (2015-2019) on patients with primary colon cancer and synchronous liver metastases. The main exposure was neoadjuvant chemotherapy before simultaneous resection of colon cancer and hepatic metastases. Propensity-score matching was used to match patients who had upfront surgery without neoadjuvant chemotherapy with patients who received neoadjuvant chemotherapy. The primary outcome was 5-year overall survival (OS). Secondary outcomes included hospital stay, 30-day and 90-day mortality, 30-day unplanned readmission, conversion to open surgery, surgical margins, and disease downstaging.</span></div></div><div><h3>Results</h3><div>Overall, neoadjuvant chemotherapy was given to 38.3% of 4060 patients. After matching, 1446 patients (53% male) were included; 482 were in the neoadjuvant group and 964 were in the no-neoadjuvant group. Neoadjuvant chemotherapy was associated with a longer restricted mean OS (46.7 vs. 40.6 months, <em>P</em> &lt; .001) and significantly lower rates of 90-day mortality (3% vs. 6.5%, <em>P</em> = .008), 30-day unplanned readmission (4.8% vs. 8.8%, <em>P</em> = .002), positive surgical margins (6.5% vs. 15.1%, <em>P</em> &lt; .001), and administration of adjuvant therapy (47.3% vs. 79.5%, <em>P</em> &lt; .001). The 2 groups were comparable in hospital stay, 30-day mortality, and number of examined lymph nodes.</div></div><div><h3>Conclusions</h3><div>Giving neoadjuvant chemotherapy before simultaneous resection of colon cancer and hepatic metastases was associated with extended mean OS and reduced rates of 90-day mortality, 30-day unplanned readmission, and positive surgical margins.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 3","pages":"Pages 400-409.e1"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Real-World Outcomes of First Line EGFR Inhibitor Use, Cetuximab Versus Panitumumab, in Patients with Left-Sided, RAS Wild-Type, Metastatic Colorectal Cancer","authors":"Jane McKenzie ,&nbsp;Vanessa Wong ,&nbsp;Shehara Mendis ,&nbsp;Rachel Wong ,&nbsp;Suzanne Kosmider ,&nbsp;Yat Hang To ,&nbsp;Louise Nott ,&nbsp;Jeremy Shapiro ,&nbsp;Javier Torres ,&nbsp;Belinda Lee ,&nbsp;Azim Jalali ,&nbsp;Stephanie Hui-Su Lim ,&nbsp;Susan Caird ,&nbsp;Adnan Khattak ,&nbsp;Peter Gibbs","doi":"10.1016/j.clcc.2025.04.001","DOIUrl":"10.1016/j.clcc.2025.04.001","url":null,"abstract":"<div><h3>Background</h3><div><span>Epidermal growth factor receptor inhibitors<span> (EGFRi), most commonly cetuximab<span> and panitumumab, are first-line options for patients with left-sided, RAS wildtype (RASwt) </span></span></span>metastatic colorectal cancer. Limited data is available comparing EGFRi outcomes.</div></div><div><h3>Methods</h3><div>Data for patients diagnosed January 2015 to October 2024 was reviewed from TRACC, a prospective, multi-site Australasian colorectal cancer registry. Patients with left-sided, RASwt disease treated with an EGFRi as first-line (1 L) therapy were identified. Survival outcomes were calculated using Kaplan-Meir methods.</div></div><div><h3>Results</h3><div><span><span>We identified 747 patients with RASwt, left-sided, metastatic colorectal cancer. Of these, 287 (38%) received 1 L therapy that included </span>cetuximab (</span><em>n</em><span> = 210, 73%) or panitumumab (</span><em>n</em><span> = 77, 27%). A switch from one to the other agent occurred in seven patients, all due to skin toxicity, including six patients (7.8%) initially treated with panitumumab and 1 (0.5%) initially treated with cetuximab. After switching, median time on the second EGFRi agent was 212 days. For 242 patients treated with an EGFRi in combination with doublet chemotherapy, toxicity contributed to treatment cessation more often in patients treated with panitumumab (32% vs. 13%, </span><em>P</em> = .003). For the subset of patients treated with palliative intent (<em>n</em> = 156), median progression-free (<em>P</em><span> = .43) and overall survival (</span><em>P</em> = .98) were similar for both EGFRi.</div></div><div><h3>Conclusion</h3><div>In this real-world analysis, a switch from one EGFRi agent to the other in the presence of skin toxicity led to durable treatment benefit with the alternate EGFRi. For patients receiving first-line cetuximab or panitumumab in combination with doublet chemotherapy, toxicity-related treatment cessation rates differed between EGFRi agents. No differences were seen in survival outcomes.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 3","pages":"Pages 362-368"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Relevance of ctDNA RAS Mutation in Patients With Metastatic Colorectal Cancer Treated With Cetuximab","authors":"Seong-Eun Kim ,&nbsp;Ji Sung Lee ,&nbsp;Sun Young Kim ,&nbsp;Jeong Eun Kim ,&nbsp;Yong Sang Hong ,&nbsp;Tae Won Kim","doi":"10.1016/j.clcc.2025.03.002","DOIUrl":"10.1016/j.clcc.2025.03.002","url":null,"abstract":"<div><h3>Background</h3><div>RAS mutations are important biomarkers for predicting the efficacy of anti-EGFR treatment in metastatic colorectal cancer (mCRC). The emergence of RAS mutations is a known resistance mechanism. This study aimed to evaluate the prognostic significance of circulating tumor DNA (ctDNA) RAS mutations in patients with mCRC treated with cetuximab, focusing on the temporal dynamics of RAS mutation emergence.</div></div><div><h3>Patients and Methods</h3><div>Patients with tissue-confirmed RAS wild-type mCRC were included in the study. ctDNA samples were collected at baseline, every 8 weeks during treatment, and after the final cetuximab dose. Cetuximab, combined with FOLFOX or FOLFIRI, was administered as first-line therapy. The primary objective was to assess the impact of emergent ctDNA RAS mutations on progression-free survival (PFS) during cetuximab-based treatment in the first-line setting.</div></div><div><h3>Results</h3><div>A total of 49 patients contributed at least 1 ctDNA sample, with 320 samples collected in total. The baseline concordance rate between ctDNA and tissue RAS status was 89.1% (41/46). Among 41 baseline RAS wild-type cases, 22 (53.7%) demonstrated emergent RAS mutations. The median time to RAS emergence was 12.8 months, and the median PFS was 12.7 months. Temporal analysis revealed that a single detection of RAS mutation was not consistently associated with poor PFS and could resolve in subsequent tests. However, time-dependent analysis indicated that the presence of ctDNA RAS mutations at any time point was significantly associated with poorer PFS (adjusted HR = 2.24, <em>P</em> = .02).</div></div><div><h3>Conclusion</h3><div>The emergence of ctDNA RAS mutations during cetuximab-based first-line therapy exhibits temporal variability. Nevertheless, the presence of ctDNA RAS mutations at any time point is collectively associated with reduced PFS.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 3","pages":"Pages 341-351.e5"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}